PROTEINS BY DESIGN XMAB ANTIBODY & CYTOKINE THERAPEUTICS - CORPORATE OVERVIEW JANUARY 2022
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Proteins by Design® XmAb® Antibody & Cytokine Therapeutics Corporate Overview January 2022
Forward-Looking Statements Certain statements contained in this presentation, other than statements of historical fact, may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding Xencor's development plans and timelines; potential regulatory actions; expected use of cash resources; the timing and results of clinical trials; the plans and objectives of management for future operations; and the potential markets for Xencor's product and development candidates. Forward-looking statements are based on the current expectations of management and upon what management believes to be reasonable assumptions based on information currently available to it, and involve numerous risks and uncertainties, many of which are beyond Xencor's control. These risks and uncertainties could cause future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Such risks include, but are not limited to, potential delays in development timelines or negative preclinical or clinical trial results, reliance on third parties for development efforts and changes in the competitive landscape including changes in the standard of care, as well as other risks described in Xencor's filings with the Securities and Exchange Commission (SEC). Xencor expressly disclaims any duty, obligation or undertaking to update or revise any forward-looking statements contained herein to reflect any change in Xencor's expectations with regard thereto of any subsequent change in events, conditions or circumstances on which any such statements are based, except in accordance with applicable securities laws. For all forward-looking statements, we claim the protection of the safe harbor for forward looking statements contained in the Private Securities Litigation Reform Act of 1995. 2
Xencor: Engineering Antibody Immune
Functions to Make Better Drugs Antibody Structure
Fv Fv
• XmAb® Fc domains: small changes, big functional impacts
– Augments native immune functions and/or controls structure
– Preserves half-life, stability and production
– Over 1,000 issued patents and pending patents worldwide
• Expansive, advancing bispecific antibody and cytokine drug candidate portfolio
– 8 XmAb bispecific antibodies in Phase 1 or 2 clinical studies
– 2 XmAb cytokines in Phase 1 clinical studies
– Multiple pre-clinical programs
• Partnership portfolio leverages modular XmAb technology
– Co-development and extensive commercial rights with Genentech and Janssen
– Multiple partnerships for technology licenses: little/no effort and greatly broadens scope
XmAb® Fc
• 3 XmAb antibodies commercialized by partners; ongoing revenue generation Domains
– Ultomiris® (Alexion) multiple indications approved U.S., EU, Japan
– Sotrovimab (Vir/GSK) granted U.S. EUA and global authorizations to treat mild-to-moderate COVID-19
– Monjuvi® (MorphoSys) U.S./EU approvals for relapsed or refractory DLBCL
AstraZeneca Rare Disease
3
Layers of Value Creation Built on XmAb® Technology
Engineered Innovations within
Cytokines Bispecifics
Future waves of pipeline growth
IL-15, IL-2, IL-12 Novel targets,
are built upon technological mechanisms & formats
competitive advantage Targeted IL-15s
CD28 T cell engagers,
ENPP3, XmAb® 2+1
Clinical execution & advancement
Broad internal clinical-stage Encouraging initial data from
portfolio of 6 bispecific antibodies vudalimab, plamotamab and tidutamab
and 2 engineered cytokines support mid-stage development plans
3 products marketed by partners
XmAb® technology platforms have
enabled a strong financial foundation 16 partnerships for XmAb technology
and provided technical validation $660mm in cash & equivalents*
* 12/31/2021 estimate
4
XmAb® Fc Domains Shift Focus of Antibody Drug
Discovery by Creating New Axes for Differentiation
Standard Technology
Fv
focus
Same Fc
Soliris® Rituxan® anti-CD19 Fv Bispecifics Cytokines
antibody
XmAb Fc Engineering
Xencor Fc
Domains
Ultomiris® Monjuvi® Obexelimab XmAb XmAb
(ravulizumab) (tafasitamab/XmAb5574) Bispecifics Cytokines
5
XmAb® Fc Domains Augment Natural Antibody Functions
Natural Fc
Function
Circulating Cytotoxicity Immune regulation Stable homodimer
half-life (immune cell) Antigen clearance structure
Fc Receptor FcRn FcgRIIa, FcgRIIIa FcgRIIb N/A
Fc Domain
Redesigns
XmAb Xtend™ Cytotoxic Immune Inhibitor Bispecific
Enhanced Domain Domain Domain Domain
Function Prolonged Enhanced cytotoxicity Immune inhibition Stable heterodimer
half-life (immune cell) Rapid clearance structure
Additional Fc domains: stability, complement activation
99.5% identical to natural antibody
Plug-and-play substitution into any antibody
6
Development Focus on XmAb® Bispecifics and Cytokines
Program Fc Commercial
Indications Preclinical Phase 1 Phase 2 Phase 3
(Targets/Design) Domain Rights
Vudalimab Bispecific mCRPC
PD-1 x CTLA-4 Xtend Gynecologic Tumors
Tidutamab Bispecific MCC, SCLC Phase 1b/2
SSTR2 x CD3
Plamotamab 1
Bispecific B-cell malignancies
CD20 x CD3
XmAb841 Bispecific
Oncology
CTLA-4 x LAG-3 Xtend
XmAb104 Bispecific
Oncology
PD-1 x ICOS Xtend
XmAb306 Bispecific 2
Oncology
IL15/IL15Ra-Fc Xtend
XmAb564 Bispecific
Autoimmune
IL2-Fc Xtend
XmAb968 Bispecific T-ALL, T-LBL, AML IST
CD38 x CD3
XmAb819 Bispecific
Renal cell
ENPP3 x CD3 (2+1) carcinoma
XmAb808 Bispecific Prostate cancer,
B7-H3 x CD28 Xtend Oncology
XmAb662 Bispecific
Oncology
IL12-Fc Xtend
1 Co-development 2 Co-development with Genentech; 45% P&L share; option to co-promote in U.S.
with Janssen; 20% development cost share; option to co-detail
7
Progress Across Portfolio Segments Leading to
Value Creating Milestones in 2022
Segment 2021 2022
Entered Janssen plamotamab/CD28 collaboration Initiate potentially registration-enabling Phase 2 study
of plamotamab in combination with tafasitamab and
Presented additional Phase 1 data from lenalidomide, in r/r DLBCL
plamotamab in NHL Present data from plamotamab Phase 1 monotherapy
T Cell Announced longer follow-up and additional biomarker expansion cohorts in 2H 2022
Engagers analysis from Phase 1 of tidutamab in NET Incorporate subcutaneous administration into ongoing
(CD3, CD28) Initiated Phase 1b/2 study of tidutamab for Phase 1 study of plamotamab
Merkel cell carcinoma and small-cell lung cancer Initiate Phase 1 study of XmAb819 in RCC
Submitted IND for XmAb819 (ENPP3 x CD3) for Submit IND for XmAb808 (B7-H3 x CD28)
renal cell carcinoma Initiate Phase 1 study of XmAb808 in solid tumors
Announced maturing Ph1 data from vudalimab in Initiate Phase 2 study of vudalimab in high-risk mCRPC
TME CRPC, RCC and tumors without approved CPIs and certain gynecologic malignancies
Activators Initiated Phase 2 study of vudalimab in mCRPC
Present initial data from the Phase 2 study of
vudalimab in mCRPC in 2H 2022
Present data from XmAb564 healthy volunteers study
Presented early, high-level data from XmAb306
(IL15/IL15a-Fc) Initiate Phase 1 multiple-ascending dose study
Engineered of XmAb564 in select autoimmune diseases
Cytokines Announce new clinical studies of XmAb306 with other
Initiated Phase 1 healthy volunteer study of
agents (e.g., NK or T-cell recruiting)
XmAb564 (IL2-Fc) for autoimmune disease
Submit IND for XmAb662 (IL-12-Fc)
Amgen guides to development plans for AMG 509
Worldwide authorizations for Vir/GSK’s sotrovimab
Select (STEAP1 x CD3) XmAb® 2+1 bispecific antibody in
Partner Minjuvi® (tafasitamab) approved in EU prostate cancer
Programs Vir/GSK’s sotrovimab continued use against SARS-CoV-2
Licensed obexelimab to Zenas BioPharma omicron and new variants
8
XmAb® Products Marketed by Partners Provide
Three Royalty Streams
XmAb Fc Commercial
Domain Medicine Indications Rights/Partners
Paroxysmal nocturnal hemoglobinuria
(PNH) or atypical hemolytic uremic
syndrome (aHUS) to inhibit
complement-mediated thrombotic AstraZeneca Rare Disease
microangiopathy (TMA)
Xtend™
Emergency Use Authorization (EUA) for
Fc Domain
the Treatment of COVID-19
In combination with lenalidomide for
the treatment of adult patients with
relapsed or refractory DLBCL not
otherwise specified, including DLBCL
arising from low grade lymphoma, and
who are not eligible for autologous
Cytotoxic stem cell transplant (ASCT)
Fc Domain
Minjuvi® (global)
9
XmAb® Fc Domains Create Numerous Differentiated
Antibodies for Technology Partners
Fc Commercial
Selected Programs Indications Preclinical Phase 1 Phase 2 Phase 3 Marketed
Domain Rights
Ultomiris® Xtend™ PNH, aHUS
AstraZeneca Rare Disease
Monjuvi®
Cytotoxic DLBCL
(tafasitamab/XmAb5574)
Sotrovimab Xtend COVID-19 EMERGENCY USE AUTHORIZATION (FDA)
(VIR-7831)
Cytotoxic
VIR-3434 Hepatitis B
Xtend
SARS-CoV-2 mAb Duo Xtend COVID-19
Immune Autoimmune
Obexelimab
Inhibitor Disease
Immune
AIMab7195 Food Allergy
Inhibitor
VIR-2482 Xtend Influenza A
XmAb bispecific Bispecific Oncology
AMG 509 2+1 Prostate
STEAP1 x CD3 Bispecific cancer
XmAb bispecific Bispecific Oncology
XmAb bispecific Prostate
Bispecific
TAA x CD28 cancer
Technology licensing expands pipeline with very little opportunity cost
Registered trademarks: Ultomiris® (Alexion Pharmaceuticals, Inc.), Monjuvi® (MorphoSys AG).
10XmAb® Bispecific Fc Domain Enabling New Classes of Biologics and Therapeutic Mechanisms of Action
Plug-and-play Fc Domain Enables Rapid Prototyping of
Target Combinations and Pipeline Generation
XmAb®
XmAb®
Bispecific
Cytokines
Antibodies
XmAb® Bispecific Fc Domains Retain Beneficial Antibody Properties
Highly stable, modular scaffold
Antibody-like half-life in vivo
Enable Multiple Classes
of New Biologics
Compatible with standard manufacturing
and development processes
12Distinct and Novel Mechanisms-of-Action
Enabled By XmAb® Bispecific Domain
T Cell Engager Dual Checkpoint/Co-stim Cytokine-Fc
Vudalimab
CTLA-4
Cytotoxic Cytotoxic
T Cell T Cell PD-1
CD3 or
CD28
nivo, pembro
TAA (CD20,
SSTR2, B7-H3, etc.)
IL15 IL15Ra IL15/
anti-X
IL15Ra
Cytotoxic
T Cell
Tumor Cell
XmAb306 Targeted Cytokine
XmAb841
13XmAb® Bispecific Antibodies Against CD28 Provide
Tumor-Specific T Cell Activation Boost
T Cell Engager
Classic interaction between T cell and Interaction between T cell and tumor cell
antigen presenting cell (APC) amplified with CD28 bispecifics
CD3 Bispecific or
(Signal 1) Checkpoint Inhibitor
CD3
TCR MHC
2
TAA
CD28
(Signal 2)
CD28 × TAA
CD28 co-stimulation promotes tumor-specific activation and proliferation
Low affinity, monovalent binding designed to avoid historic safety concerns (superagonism)
14XmAb® Engineered Cytokines
XmAb® Cytokines: Potency-tuned to Enhance
Half-life and Tolerability
Reduced affinity
toxicity • Receptor selectivity
• ↑Half-life
native cytokine
activity
XmAb potency-optimized XmAb Fc
cytokine-Fc • ↑Half-life
• ↑Stability
• Modular
• Enables targeting
Time →
Xencor’s general approach for creating cytokine therapies
• Overcomes native cytokine short half-life and high toxicity
• Systematically engineering broad portfolio of cytokines
16Growing Portfolio of XmAb® Cytokines
XmAb306 XmAb564 XmAb662 XmAb Targeted IL-15
IL12-p35
anti-X
IL-2 IL12-p40
Cytokine IL-15/IL-15Ra (Treg selective) IL-15/IL-15Ra
XmAb®
Bispecific
Fc Domain
Cell Targets Cytotoxic NK, T cells Regulatory T cells IFNg secreting NK, T cells Immune marker defined
Indication Oncology Autoimmune Disease Oncology Oncology
Phase 1 Phase 1 Preclinical stages
Status IND in 2022
Dose Escalation Dose Escalation
2 clinical-stage XmAb® Cytokines, more in IND-enabling and preclinical stages
Engineered to expand select immune cell populations
Designed to be tolerable, active, easy to use
17XmAb®306: IL-15 with Long Half-life, Improved Tolerability
and Extended T and NK Cell Stimulation in NHP Models
Tolerability in NHPs PK in NHPs
0
10
XmAb306
re la tiv e s e ru m c o n c e n tra tio n
Engineered IL15Rα 10 -1 XmAb306
IL15
-2
10
wt-Fc wt-Fc
-3
10
0 2 4 6 8 10
D ays post dose
In vivo pharmacodynamics
C D 8 T c e lls C D 1 6 + N K c e lls
10 10
Xtend 8 8
fo ld in c r e a s e
fo ld in c r e a s e
Bispecific Fc 6 6
XmAb306
4 4
XmAb306
XmAb306 2
wt-Fc
2
wt-Fc
0 0
0 5 10 15 0 5 10 15
D ays p ost d ose D ays p ost d ose
Potential to enhance activity of both NK therapies (Rituxan, Herceptin, allo NK cells, etc.)
and T cell therapies (checkpoint inhibitors, cell therapies)
Ongoing Phase 1: monotherapy and combination with atezolizumab (PD-L1) in advanced solid tumors
Co-development with Genentech; 45% worldwide P&L share; option to co-promote in U.S.
18XmAb®306 Promotes High Levels of Sustained NK Cell
Expansion in Ongoing Phase 1 Dose-Escalation Study
Encouraging preliminary data announced in November 2021
• Consistent and robust dose-dependent NK cell expansion and accumulation upon repeat dosing has
been observed for multiple NK cell subsets, including mature NK cells. Significant NK cell expansion
and accumulation was observed beginning in lower dose cohorts, and at higher dosing cohorts NK
cell expansion has reached 40- to 100-fold higher levels than baseline and has been sustained for
weeks throughout dosing.
• Unconfirmed RECIST responses have been observed in multiple tumor types, including in a patient
treated with XmAb306 monotherapy.
• The study has reached dose levels that promote T cell activity, and evidence of peripheral effector T
cell proliferation has been observed.
• Generally well tolerated as both a monotherapy and in combination with atezolizumab. No DLTs or
treatment-related SAEs have been observed to date. Dose escalation continues for both monotherapy
and in combination with atezolizumab.
• XmAb306 has a multi-day circulating half-life, which is consistent with its reduced-potency design and
data generated in preclinical studies.
Announce new clinical studies of XmAb306 in combination with other agents,
such as NK or T-cell recruiting therapies, in 2022
19XmAb®564: IL-2 with Long Half-life, Improved Tolerability
and Selectivity for Treg Activation in NHP Models
In vivo pharmacodynamics (NHPs)
IL2
Selectivity design
↓IL2R - lower potency
↑IL2Rα – Treg bias
Xtend
Bispecific Fc
XmAb564
Monovalent design to avoid undesired activation
Treg amplification has potential in numerous autoimmune
diseases – use of native IL-2 limited by toxicity and poor Pharmacokinetics (NHPs)
1000
selectivity XmAb27564 1X Dose
100 XmAb27564 3X Dose
Phase 1, single-ascending dose trial in healthy volunteers WT-IL2-Fc 1X Dose
10
• Assessing PK, safety, biomarkers of activity
(Treg vs. T effectors) 1
• Subcutaneous delivery
0.1
0 6 12 18 24 30 36
Phase 1, multiple-ascending dose trial in patients (2022 start) Days
20XmAb®662: IL-12 with Long Half-life, Improved
Tolerability and Potent Immune Stimulation
IL12-p35 Strong anti-tumor activity (mice)
IL12-p40
250
Tumor Volume (mm3)
200 wt
150
XmAb662
100
0.1 mg/kg
50
Xtend 0
0 2 4 6 8 10 12 14 16 18 20 22 24
Bispecific Fc
-50 Days Post Dose 1
XmAb662
Superior PK (NHPs)
Concentration (ng/mL)
100,000
10,000
XmAb662
Highly immune stimulating – IFNg secretion, activation 1,000 1 mg/kg
of NK and CD8 T cells 100
Native IL-12 therapy active in multiple tumor types, but toxic 10
wt
1
Gradual activity build up for potential improved tolerability 0 5 10 15
Time (days post dose)
IND planned in 2022, IND-enabling studies ongoing
21XmAb® Bispecific Antibodies Tumor Microenvironment Activators Vudalimab (PD-1 x CTLA-4) Updated Preliminary Phase 1 Data SITC 2021
XmAb® Dual Checkpoint/Co-Stim Bispecifics Have Distinct
Mechanisms to Stimulate the Tumor Microenvironment
Vudalimab (XmAb®717)
PD-1 • PD-1 x CTLA-4 bispecific
• Selective for PD-1/CTLA-4 double-
positive cells → potential improved
CTLA-4 tolerability
• Phase 2 initiated in prostate cancer
• Phase 2 initiated in gynecologic
XmAb®306 tumors and high-risk mCRPC
• Synergizes with dual PD-1
nivo,
checkpoint/co-stim
pembro
XmAb®841
LAG-3 • CTLA-4 x LAG-3 bispecific
• Combinable with anti-PD-1 for
triple checkpoint blockade
CTLA-4 • Phase 1 ongoing
PD-1 XmAb®104
• PD-1 x ICOS bispecific
• Synergistic T-cell stimulation
ICOS • Phase 1 ongoing
23XmAb® Dual Checkpoint/Co-Stim Bispecifics are
Designed to Promote Tumor-Selective T Cell Targeting
Periphery Tumor Environment
Weak monovalent interactions Strong bivalent interactions on
on single-positive cells double-positive cells TIL Activation
No Activation
2nd Tumor
checkpoint
only
Double-
positive TILs
PD1
only • Tumor infiltrating lymphocytes (TILs)
coexpress multiple checkpoints (Matsuzaki
2010, Fourcade 2012, Gros 2014)
• Bivalent binding increases avidity
24Vudalimab: Selective PD-1 x CTLA-4 Inhibition to Enable
Dual Checkpoint Inhibition in Broad Range of Indications
Phase 2 metastatic castration resistant Clinical Activity Across Multiple Tumor Types
prostate cancer (mCRPC) started Q3 2021
• Patients stratified by molecular subtype
• Combination or monotherapy, depending
on subtype
mCRPC rationale
• Initial data from vudalimab Phase 1 study
• Limited checkpoint inhibitor competition
• High unmet need
• CTLA-4 blockade historically associated
SITC 2021
with increased response rates
Second Phase 2 study: gynecologic Activity in multiple tumor types in patients with prior
tumors & high-risk mCRPC starting up treatment with checkpoint inhibitors
Generally well tolerated throughout expansion cohorts, most
• CR in BRCA+, serous ovarian cancer common adverse events were immune-related rash and
patient in Phase 1 transaminase elevations
• PRs in high-risk mCRPC patients (n=2/4 Lower rates of some types of immunotherapy-related adverse
events, including colitis, than are typically seen with CTLA-4
evaluable and with measurable disease) in blockade
Phase 1
25Vudalimab Was Generally Well Tolerated;
Most Common Adverse Events Were Immune Related
Immune-related adverse events reported for
≥3 patients at the 10 mg/kg dose (n=110)
Rash
Pruritus
Transaminases increased
Diarrhea
Hypothyroidism
Infusion related reaction
Myalgia
Acute kidney injury
Hyperglycemia
Blood creatinine increased
Pneumonitis
Blood bilirubin increased
Lipase and amylase increased
Lipase increased alone
Adrenal insufficiency
Pancreatitis
Immune-mediated pancreatitis (Grade 5) was reported for one patient with RCC, whose cancer had
already metastasized to the pancreas at baseline and progressed on study. Grade 5 myocarditis and
respiratory failure were reported for a patient with NSCLC who had a history of significant cardiac
SITC 2021 events, including atrial fibrillation and the insertion of a dual-chamber pacemaker.
26Clinical Activity Across Multiple Tumor Types in Patients Who
Had Previously Been Treated With a Checkpoint Inhibitor
The objective
response rate
across 10 mg/kg
cohorts was
14.1% (11/78).
The median duration of response for all responders was 18.3 weeks (unadjusted).
The median duration of response for patients with RCC was 24.1 weeks (unadjusted),
and two RCC patients remained on treatment.
SITC 2021
27Efficacy Analysis: Responses in CRPC & Ovarian Cancer
Provide Rationale for Phase 2 Clinical Development
Complete responses Partial responses
A complete response was Several partial responses observed in melanoma (n=2), RCC (n=3), NSCLC
observed in a patient with (n=2) and CRPC (n=2). All responses in patients with melanoma and CRPC and
BRCA1+ high-grade serous two responses in patients with RCC were confirmed. All responders, except those
ovarian cancer, who had received with CRPC, had received prior checkpoint inhibitor therapy.
multiple prior treatments,
including olaparib and nivolumab
in the metastatic setting. The
patient had a partial response after Encouraging clinical activity in prostate cancer
Cycle 4, and by Cycle 18 of
treatment all lesions had resolved Of the 12 efficacy-evaluable patients with CRPC, 4 had measurable disease
except a lesion in the abdominal and follow-up RECIST assessments, including the 2 CRPC responders.
wall, which later showed no cancer
cells upon biopsy.
The two CRPC responders had visceral and nodal metastases, had response
durations of 41.3 and 27.0 weeks, were without progression on bone scans and
A confirmed complete response was
had confirmed prostate-specific antigen (PSA) reductions of more than 50% from
observed in a patient with
baseline. Among twelve patients with baseline and follow-up PSA assessments,
melanoma during dose-escalation at
including the two responders, 33% (4/12) had PSA reductions greater than 50%.
the 10 mg/kg dose level.
SITC 2021 Efficacy analysis included 78 evaluable patients receiving any amount of vudalimab, who had been followed for at least two cycles prior to data cut.
28XmAb® Bispecific Antibodies CD3 and CD28 T Cell Engagers
XmAb® T Cell Engagers Use Multiple Formats and
Affinity Designs to Customize for Each Tumor Target
XmAb® 1+1 XmAb® 2+1
Tumor antigen (e.g., ENPP3, STEAP1)
Tumor
Antigen Tuned 2+1 Format = Selective Reactivity
(e.g., CD20)
CD3
CD3
5 clinical-stage
CD3 programs
• AMG 509
<
• XmAb819
CD3 affinity tuned for reduction of cytokine release syndrome and off-tumor cell killing
Tumor antigen binding affinity tuned for tumor expression density and to match format
30Plamotamab: Leading the Creation of Highly Active,
Chemo-free Antibody Combinations in Lymphoma
• Plamotamab (CD20 x CD3) generally well tolerated and demonstrates encouraging
monotherapy activity at intravenous Phase 2 dose – 50 mg flat dosing every two weeks
following step-up dosing
• PK modeling supports subcutaneous administration; incorporating into ongoing Phase 1
Monotherapy activity supports the potential for a differentiated safety profile
and better outcomes for patients when plamotamab is combined
with other agents in a chemotherapy-free regimen:
Unique chemo-free combination with Janssen worldwide license to plamotamab; two-year
tafasitamab (Monjuvi®) and lenalidomide research collaboration to create novel XmAb® CD28
• Recruits distinct and complementary cytotoxic bispecifics targeted against certain B cell targets
immune cells, T cells and Natural Killer cells, • Potential to amplify the activity of plamotamab and other CD3
against tumor cells bispecifics with targeted, tumor-selective co-stimulation
• Phase 2 in relapsed/refractory diffuse large B cell • Plamotamab: Mid-teen to low-twenties royalties; 20% development
lymphoma (DLBCL) planned to start in early 2022 cost-sharing; option for 30% co-detail
• Phase 1b studies also planned in frontline DLBCL, • CD28 bispecifics: High-single to low-double digit royalty; option to
r/r follicular lymphoma fund 15% of development costs for increased royalties; option for
30% co-detail
31Monotherapy Safety, Tolerability and Activity Support
Novel Combination Development Plans
Phase 1 Part C Results at RP2D Part B + C Tumor Response – DLBCL and FL (n=47)
Heavily pretreated patients (n=14)
• Median 4 prior therapies for FL (n=4)
Best % Change from Baseline
• Median 5 prior therapies for DLBCL (n=8)
Plamotamab generally well tolerated
• No Grade 3/4 CRS events
• Safety events generally mild, moderate in
severity
@ = Cohort Part C
Encouraging response rates
• 100% ORR (4/4) in FL, and CRs were
observed in two patients (50%)
• 40% ORR (2/5) in DLBCL, and a CR was Median duration of response for the overall population of weight-
observed in one patient (20%) based dosing cohorts and Part C was 225 days for DLBCL and
171 days for FL.
• All 5 evaluable patients with DLBCL received
prior CAR-T therapy, and two evaluable
patients with DLBCL received prior NK cell Expansion groups in DLBCL and FL now open
therapy to evaluate safety and efficacy of plamotamab
monotherapy at RP2D
• Data from expansion cohorts planned for 2H 2022
RP2D = Recommended Phase 2 Dose
ASH 2021
32Differentiated Chemo-free Combination Strategy to
Develop Plamotamab in Lymphoma
Plamotamab + Tafasitamab Plamotamab + B Cell x CD28 Bispecific
• Targets two different highly expressed • Novel mechanism to amplify T-cell cytotoxicity
B-cell antigens, CD19 and CD20, by binding CD28 to activate co-stimulation
to potentially avoid resistance due to pathways in a targeted, tumor-selective
antigen loss manner
• Recruits distinct and complementary • Offers additional level of control over CD3
cytotoxic immune cells, T cells and bispecific T-cell activation, offering potentially
Natural Killer cells, against tumor cells reduced toxicity and higher tumor killing
T Cell B-cell Tumor NK Cell T Cell B-cell Tumor
Two Complementary Anti-Tumor Mechanisms Amplified T-cell Cytotoxicity
33Tidutamab: SSTR2 x CD3 Antibody in Solid Tumor
Indications with High Unmet Need
Acute & Sustained T Cell Proliferation
Phase 1b/2 study initiated Q3 2021 in small cell lung
cancer (SCLC) and Merkel cell carcinoma (MCC)
• SSTR2-expressing tumor types known to be
responsive to immunotherapy
Phase 1 data update in neuroendocrine tumors (NET)
presented at NANETS, October 2021
• 21 patients in dose-escalation, 20 patients in expansion
• Heavily pre-treated: 50% received prior radionuclide Acute & Sustained T Cell Activation
• Stable disease in 27%
• Generally well tolerated; CRS observed in 41% of
patients, nearly all Grade 1/2
• CD8+ effector T cells showed a dose-dependent and
persistent increase in proliferation activity marker Ki67
• Higher baseline intratumoral PD-L1 expression and
increases on treatment were associated with a shorter
time on study
34Novel Tumor Targets and Immune Activation Differentiate
Next Clinical Bispecific Antibodies (e.g., ENPP3, CD28)
XmAb819 (ENPP3 x CD3) XmAb808 (B7-H3 x CD28)
Selective T cell directed cytotoxicity Enhanced, selective T cell activation through CD28
On-target cell line
Off-target cell line
• Tumor-specific boost to T cells (Signal 2)
• Renal cell tumor antigen ENPP3 also • B7-H3 enables potentially broad solid tumor
expressed at low levels on normal tissue use; high expression in prostate cancer
• Multi-valent XmAb 2+1 format for • IND submission planned in 2022
selective high-density ENPP3 binding
• Reduced potency CD3 binding to improve Janssen collaboration for CD28 bispecific antibody
rates/severity of cytokine release syndrome against an undisclosed prostate target opens access
• IND submitted in December 2021 to prostate-cancer franchise for clinical combinations
35Layers of Value Creation Built on XmAb® Technology
2022 Milestones
Announce new clinical studies of XmAb306 with other agents
Technological Competitive Advantage (e.g., NK or T-cell recruiting)
Creates Future Pipeline Growth Present data from XmAb564 healthy volunteers study
Initiate Phase 1 multiple-ascending dose study of XmAb564
Tumor-selective
Engineered Multi-valent in select autoimmune diseases
CD28 Bispecific
Cytokines Antibodies Formats Initiate Phase 1 study of XmAb819 in RCC
Submit IND and initiate Phase 1 study of XmAb808 (B7-H3 x CD28)
Submit IND for XmAb662 (IL-12-Fc)
Initiate vudalimab Phase 2 study in high-risk mCRPC and certain
Clinical Execution & Advancement gynecologic malignancies
Present initial vudalimab Phase 2 study data in mCRPC in 2H22
Encouraging initial data from
vudalimab, plamotamab and tidutamab Initiate potentially registration-enabling Phase 2 study of plamotamab in
support mid-stage development plans combination with tafasitamab and lenalidomide, in r/r DLBCL
Present plamotamab Phase 1 monotherapy expansion cohort data in 2H22
Incorporate subcutaneous admin in ongoing plamotamab Phase 1 study
Strong Financial Foundation &
Technical Validation
Amgen guides to development plans for AMG 509 (STEAP1 x CD3)
3 products marketed by partners XmAb® 2+1 bispecific antibody in prostate cancer
16 partnerships for XmAb technology Vir/GSK’s sotrovimab continued use against SARS-CoV-2
omicron and new variants
$660mm in cash & equivalents*
* 12/31/2021 approximation
36Proteins by Design® XmAb® Antibody & Cytokine Therapeutics Corporate Overview January 2022
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